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Positive and negative feedback loops are crucial for regulating biological signaling systems. These feedback loops are processes that connect output signals to their inputs.

Negative feedback loops

Most signaling systems have negative feedback loops that can perform different functions such as output limiter, and adaptation.

Output limiter

Upon receiving an input signal, the cellular response rapidly increases until a threshold is reached. Beyond this threshold, a negative feedback loop stabilizes the response. For example, rapid Ca2+ uptake by the mitochondria triggers negative feedback to limit and stabilize Ca2+ concentration in the cytosol even when the signal for uptake persists.


Negative feedback mechanisms allow cellular systems to adapt to small changes in input signals. The adaptation can occur due to receptor inactivation, where the binding of signaling molecules can induce temporary sequestration of the receptors. For example, GPCRs involved in chemotaxis are down-regulated when not required.

Positive feedback loops

The positive feedback loop in a cell performs different functions such as signal amplification and response time modulation.

Signal amplification

Positive feedback loops amplify an initial signal in a relative or absolute manner. For example, when four molecules of IP3 bind to its receptor, the Ca2+ channel on the ER is partially activated to release Ca2+. The released Ca2+ triggers a positive feedback loop, fully activating the channel and releasing more Ca2+ ions.

Response time modulation

Positive feedback can change the response timing by accelerating or prolonging the time for the signaling system to generate a response. For example, positive feedback accelerates the response by opening IP3-gated Ca2+ ion channels, rapidly achieving a saturating concentration.

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